Robot-Assisted Cervical Esophagectomy: a safety and feasibility multicenter trial

Transthoracic esophagectomy with 2-field lymphadenectomy is the standard of
surgical care for patients with esophageal cancer. Though the rate of pneumonia
has significantly reduced by the implementation of minimally invasive
esophagectomy (MIE), the incidence of pulmonary complications after MIE still
ranges between 15-30%. An important risk factor for pulmonary complications is
the need for single-lung ventilation during transthoracic esophagectomy . One
of the possible approaches to reduce pulmonary complications is to adopt the
transhiatal esophagectomy which avoids thoracic access and therewith
single-lung ventilation. However, several limitations apply to a transhiatal
approach. First, the esophagus is removed blindly out of the esophagus bed.
Second, a transhiatal approach is inferior compared to a transthoracic approach
in terms of mediastinal lymphadenectomy. A relatively new approach is the RACE
procedure whereby the esophagus is mobilized through cervical access, bypassing
thoracic access and thus the need for single lung ventilation. The added value
of this procedure over a transhiatal approach is that the esophagus could be
removed under direct camera vision and it is hypothesized that a (limited)
mediastinal lymphadenectomy might be possible, which is not the case with a
transhiatal approach. To date, only few studies published on the RACE procedure
which reflect the novelty of this approach . We have published a review and
found 5 studies reporting on the RACE procedure of which 2 studies are
case-series and 3 cadaver studies . The first case series included 6 patients
of which the majority had a tumor in the mid esophagus. The upper and middle
mediastinum were reached by transcervical access and the lower mediastinum by
transhiatal access. A median of 20 thoracic lymph nodes were dissected. There
was no need for conversion. Postoperatively, 1 patient developed a pneumonia
and 1 patient a stump leakage of the gastric conduit, both Clavien Dindo grade
II. Two patients had a paralysis of the right recurrent laryngeal nerve. There
was no mortality. The most recent case series included 4 patients who underwent
the RACE procedure. The upper mediastinum was reached by transcervical access
and the lower and middle mediastinum by transhiatal access. Postoperatively, 1
patient developed a pneumonia, 1 patient an anastomotic leakage and 1 patient
had a recurrent laryngeal nerve palsy. Both case series concluded that RACE was
oncologically safe with adequate lymphadenectomy and radical resections (R0) in
all the patients. Although the current evidence is promising, it is too early
to make statements about its safety and feasibility. Therefore, the current
prospective pilot study aims to investigate the feasibility and safety of
performing RACE in patients with esophageal cancer who have a contra-indication
for transthoracic esophagectomy.

To assess the safety and feasibility of performing a robot-assisted cervical
esophagectomy (RACE) for patients with esophageal cancer.

This is a prospective multicenter phase II single-arm safety and feasibility
trial. Included patients may or may not undergo neoadjuvant therapy according
to current policies in the Netherlands and Germany, followed by RACE.

All included patients will undergo a robot-assisted transcervical esophagectomy
with abdominal and low paraesophageal lymphadenectomy, gastric conduit
reconstruction and a cervical anastomosis. The procedure starts with an
abdominal phase, performed laparoscopically or robot-assisted. Mobilization of
the stomach, abdominal lymphadenectomy and gastric conduit formation is
performed. The second phase of the operation is the transcervical dissection.
The patient is placed in supine position with the head slightly stretched to
the right. The procedure starts with a 4cm incision over the left side of the
neck. Cervical access can be achieved by the use of a commercially available
single port. Generally, a robotic camera with two robotic instruments are
inserted via the cervical access ports for dissection. First, the left side of
the cervical and thoracic esophagus is mobilized. The intercarotid fascia forms
the dorsal plane of the dissection. By using this plane, safe distance is kept
from the left recurrent laryngeal nerve (RLN) which is located in the
tracheoesophageal groove. The esophagus at the upper level of the mediastinum
is further mobilized and dissected, while the thoracic duct is identified over
the left side of esophagus. The dissection continues to the mid-thoracic
esophagus, where direct arterial branches can be encountered from the
descending aorta. At this stage, the thoracic esophagus is mobilized from the
membranous part of the trachea and carina, with exposure of the right and left
main bronchus, pulmonary vein, arch of azygos and the subcarinal nodes. In
general, this procedure is completed with a transhiatal gastric conduit pull-up
with a subsequent creation of the anastomosis at the cervical level to restore
continuity of the gastrointestinal tract.

RACE is a relatively novel approach and allows for esophagectomy by cervical
access. In 2019, an international team was set-up to investigate and develop
the RACE procedure. The team consists of prof. Van Hillegersberg, prof Ruurda,
Prof. Grimminger and Prof. Egberts. At that point, Prof. Grimminger and prof.
Egberts already had preliminary experience with the RACE procedure and
performed several cases in their hospital. The team followed a step-wise
approach to develop and safely implement the RACE procedure. First, a review
was performed to collect evidence on this topic (14). As studies showed
promising results, the next step consisted of increasing the anatomical
knowledge encountered with RACE by performing 2 anatomical cadaver studies
(21). After these studies were performed, the procedure was practiced with the
entire team on a cadaver for 3 times of which 2 sessions were hosted in the UMC
Utrecht and 1 session in Berlin. The RACE procedure was successfully performed
with the entire team. The next step is to perform this safety and feasibility
trial. As the current study was prepared in detail in recent years, the risk
caused by the RACE procedure in this study is reduced as much as possible. In
addition, the first 2 procedures will be performed under guidance of Prof.
Grimminger or Prof. Egberts. Based on literature and our own experience, we do
not have a reason to consider this procedure as dangerous or risky.

Potential benefits
- In comparison with the standard treatment, there are a few benefits to be
expected. First of all, the esophagus is removed under camera view which is not
the case during a transhiatal esophagectomy. Second, it is expected that a
limited mediastinal lymphadenectomy could be performed during the RACE
procedure, which is not the case during a transhiatal approach. A
lymphadenectomy is expected to improve the survival of patients.

Potential risks
- During the RACE procedure, damage of the recurrent laryngeal nerve palsy
could occur. This is also a known complication in 10-20% of the patients after
a standard esophagectomy. In the vast majority, patients suffer from hoarseness
which will recover over time without the need for treatment. We expect that
this complication might occur more often during the RACE procedure, but we do
not know how often exactly.